Environmental Modifications in sub-Saharan Africa: Changing Epidemiology, Transmission and Pathogenesis of Plasmodium falciparum and P. vivax Malaria Supplement Application PROGRAM SUMMARY The current Supplement application is developed under an NIH ICEMR award entitled ?Environmental Modifications in Sub-Saharan Africa: Changing Epidemiology, Transmission and Pathogenesis of Plasmodium falciparum and P. vivax Malaria? (U19 AI129326). The overarching objective of this Supplement application is to facilitate malaria control and elimination efforts in Kenya and Ethiopia, the two study countries of our ICEMR, by obtaining entomological and socio-behavioral data needed for introducing new vector control tools and by identifying optimal combinations of vector interventions to achieve the maximum impact in reducing malaria burden. The Supplement application has three projects, each with multiple specific objectives. Project 1 will evaluate the impact of spatial repellents on pyrethroid-resistant malaria vectors in MalariaSpheres, a contained semi-natural Anopheles ecosystem for studying mosquito behaviors in Kenya and Ethiopia. Project 2 will examine the social behavioral aspect of malaria vector control, especially the gaps between knowledge and mosquito control practice in the community and the underlying mechanisms for such gaps. Project 3 aims to develop an optimal malaria intervention strategy adaptive to local malaria risk, changing vector ecology, and supply chains, using a cluster randomized sequential, multiple assignment randomized trial (SMART) design. The research proposed in the Supplement application leverages the baseline data, infrastructure, and capacity established by the parent ICEMR and extends it to malaria control goal by generating data critically needed for future field trials of new mosquito control products, identifying new approaches to improve community engagement, and developing new strategies to improve the effectiveness of malaria vector control programs. As insecticide resistance is widespread in Africa and the effectiveness of the current first-line malaria vector control tools need to be improved, knowledge gained from this Supplement application will be valuable to malaria control, not only for the two countries studied under this ICEMR but also for other regions in Africa and potentially elsewhere.